DJ-1, a novel regulator of the tumor suppressor PTEN
DJ-1, a novel regulator of the tumor suppressor PTEN
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DOI：
10.1016/j.ccr.2005.02.010
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发表时间：
2005-03-01
期刊：
影响因子：
50.3
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Kim, RH;Peters, M;Mak, TW
调节细胞存活的磷脂酰肌醇3'激酶（P13'K）途径与PTEN肿瘤抑制剂拮抗。 PTEN的调节尚不清楚。果蝇的遗传筛选功能增益突变体将DJ-1识别为PTEN功能的抑制剂。在哺乳动物的细胞中，DJ-1不足会导致PKB/ AKT磷酸化降低，而DJ-1过表达导致PKB/ AKT的过度磷酸化并增加了细胞存活。在原发性乳腺癌样品中，DJ-1表达与PTEN免疫反应性负相关，并且与PKB/AKT高磷酸化相关。在19/23原发性非小细胞肺癌样品中，与配对的非肿瘤肺组织相比，DJ-1表达增加，并与复发率相关。因此，DJ-1是PTEN的关键负调节剂，可能是癌症的有用预后标记。
The phosphatidylinositol 3' kinase (P13'K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/ Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.